Activation of cellular promoters during herpes virus infection of biochemically transformed cells.

Rd, Everett

doi:10.1002/j.1460-2075.1985.tb03880.x

Cited by 70 publications

(57 citation statements)

References 49 publications

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“…Other published examples of cellular gene activation by HSV were observed after infection with wt virus (LaThangue et al, 1984;Everett, 1985;Kennedy et al, 1985;Patel et aL, 1986), suggesting that they represent a different phenomenon from that reported here. The induction of the stress response by viruses other than HSV also appears to involve a different mechanism, since wt viruses mediate the effect.…”

Section: Discussioncontrasting

confidence: 57%

Abnormal Forms of the Herpes Simplex Virus Immediate Early Polypeptide Vmw175 Induce the Cellular Stress Response

Russell

Stow

et al. 1987

Journal of General Virology

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Section: Discussioncontrasting

confidence: 57%

Abnormal Forms of the Herpes Simplex Virus Immediate Early Polypeptide Vmw175 Induce the Cellular Stress Response

Russell

Stow

et al. 1987

Journal of General Virology

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“…First, as discussed above, preclusion of ND10 disruption by overexpression of PML has no effect on viral replication in cultured cells (97). Second, this hypothesis is inconsistent with the observation that the transactivation function of ICP0 is restricted to genes introduced into the cells by transfection or infection and a specific subset of cellular genes rather than affecting a diversity of viral and cellular genes contained in the infected cell (30,72).…”

Section: Discussionmentioning

confidence: 96%

“…Despite 3 decades of research and enormous interest, it is not known how the functions encoded in ICP0 account for its phenotype in either infected or transduced cells. However, available evidence suggests that ICP0 is a multifunctional protein and that its role in viral infection reflects the sum of its multiple and diverse functions (132).Studies published nearly 20 years ago established that ICP0 activates genes introduced into cells by transfection or infection (29,30,54, 118,129). Furthermore, ICP0 also activates a specific subset of cellular genes, including several p53-responsive genes that it activates independently of p53 (72).…”

mentioning

confidence: 99%

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Role of ICP0 in the Strategy of Conquest of the Host Cell by Herpes Simplex Virus 1

Hagglund

Roizman

2004

J Virol

202

187

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In early studies, herpes simplex virus 1 (HSV-1) proteins were identified on the basis of two criteria. The first consisted of characterization of proteins contained in virions purified from cells whose proteins were labeled prior to infection. These proteins designated by the prefix VP were numbered in the order of decreasing apparent molecular weight or, conversely, ascending electrophoretic mobility in denaturing gels (147). The second criterion identified putative viral proteins accumulating in infected cells but absent from uninfected cells. These proteins, designated infected-cell proteins (ICPs), were also numbered in order of decreasing apparent molecular weight (73). One protein, however, while clearly apparent only in infected cells, varied with respect to electrophoretic mobility depending on the composition of the denaturing gel (74). This anomalously migrating protein was designated ICP0 (74). In subsequent studies, viral proteins were designated either by their known primary function (e.g., DNA polymerase, etc.) or the position of the gene along the unique long (U L ) or short (U S ) components of the viral genome (105, 107). The original ICP designation, however, was retained primarily for five proteins recognized in early studies as being the products of ␣ or immediate-early genes expressed after infection in the absence of de novo viral protein synthesis (74, 75). The five proteins, ICP0, ICP4, ICP22, ICP27, and ICP47, have been extensively studied, and for the most part, there is at least a semblance of concordance between the phenotype of cells infected with the mutant lacking the gene, the behavior of the protein in transduced cells, and the molecular functions expressed by the protein (reviewed in reference 132). ICP4 is an essential positive and negative regulator of gene expression (reviewed in reference 132). The protein blocks gene expression by binding to high-affinity DNA consensus sites located at transcription initiation sites of at least two genes. The mechanism of gene activation is less understood, although ICP4's affinity for transcription factors and binding to highly degenerate or nonconsensus sites are suggestive of how it might act. ICP27 is also a multifunctional protein whose phenotype can be largely explained by its ability to block RNA splicing but not transport of unspliced RNA early in infection and by its activity as a chaperone of newly made viral mRNA across the nuclear membranes at late times after infection (reviewed in reference 137).Available data indicate that the carboxyl-terminal half of ICP22 enables full expression of a subset of late (␥ 2 ) viral genes by causing cdc2 cyclin-dependent kinase activity to survive the degradation of its physiologic partners cyclins A and B, by an aberrant partnership with the U L 42 DNA polymerase processivity factor (2,5,6,19,141). Optimal transcription of late genes requires binding and posttranslational modification of topoisomerase II␣ by the two proteins (7). The sole known mission of ICP47 is to bind to and preclude TAP1...

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“…ICP0 is a nuclear phosphoprotein that behaves as a promiscuous activator of viral and cellular genes (7,11,28,29). ICP0 also functions as an E3 ubiquitin ligase to target several host proteins for proteasomal degradation (4,10,11,16,26).…”

mentioning

confidence: 99%

Complementation of a Herpes Simplex Virus ICP0 Null Mutant by Varicella-Zoster Virus ORF61p

Kyratsous

Walters

Panagiotidis

et al. 2009

J Virol

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The herpes simplex virus (HSV) ICP0 protein acts to overcome intrinsic cellular defenses that repress viral ␣ gene expression. In that vein, viruses that have mutations in ICP0's RING finger or are deleted for the gene are sensitive to interferon, as they fail to direct degradation of promyelocytic leukemia protein (PML), a component of host nuclear domain 10s. While varicella-zoster virus is also insensitive to interferon, ORF61p, its ICP0 ortholog, failed to degrade PML. A recombinant virus with each coding region of the gene for ICP0 replaced with sequences encoding ORF61p was constructed. This virus was compared to an ICP0 deletion mutant and wild-type HSV. The recombinant degraded only Sp100 and not PML and grew to higher titers than its ICP0 null parental virus, but it was sensitive to interferon, like the virus from which it was derived. This analysis permitted us to compare the activities of ICP0 and ORF61p in identical backgrounds and revealed distinct biologic roles for these proteins.Alphaherpesviruses encode orthologs of the herpes simplex virus (HSV) ␣ gene product ICP0. ICP0 is a nuclear phosphoprotein that behaves as a promiscuous activator of viral and cellular genes (7,11,28,29). ICP0 also functions as an E3 ubiquitin ligase to target several host proteins for proteasomal degradation (4,10,11,16,26). Through this activity, ICP0 promotes degradation of components of nuclear domain 10 (ND10) bodies, including the promyelocytic leukemia protein (PML) and Sp100. These proteins are implicated in silencing of herpesvirus genomes (9,10,22,34). Therefore, ICP0-mediated degradation of ND10 components may disrupt silencing of HSV genes to enable efficient gene expression. This hypothesis provides a plausible mechanistic explanation of how ICP0 induces gene activation.Introduction of DNA encoding the ICP0 orthologs from HSV, bovine herpesvirus, equine herpesvirus, and varicellazoster virus (VZV) can also affect nuclear structures and proteins (27). In addition, and more specific to this report, ORF61p, the VZV ortholog, activates viral promoters and enhances infectivity of viral DNA like ICP0, the prototype for this gene family (24,25). However, we have previously demonstrated two key biological differences between the HSV and VZV orthologs. We first showed that unlike ICP0, ORF61p is unable to complement depletion of BAG3, a host cochaperone protein. As a result, VZV is affected by silencing of BAG3 (15), whereas growth of HSV is altered only when ICP0 is not expressed (17). Furthermore, we have shown that while both proteins target components of ND10s, expression of ICP0 results in degradation of both PML and Sp100, whereas ORF61p specifically reduces Sp100 levels (16). These findings suggest that these proteins have evolved separately to provide different functions for virus replication.Virus mutants lacking the ICP0 gene have an increased particle-to-PFU ratio, a substantially lower yield, and decreased levels of ␣ gene expression, in a multiplicity-of-infection (MOI)-and cell-type-dependent manner (2,...

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Activation of cellular promoters during herpes virus infection of biochemically transformed cells.

Cited by 70 publications

References 49 publications

Abnormal Forms of the Herpes Simplex Virus Immediate Early Polypeptide Vmw175 Induce the Cellular Stress Response

Abnormal Forms of the Herpes Simplex Virus Immediate Early Polypeptide Vmw175 Induce the Cellular Stress Response

Role of ICP0 in the Strategy of Conquest of the Host Cell by Herpes Simplex Virus 1

Complementation of a Herpes Simplex Virus ICP0 Null Mutant by Varicella-Zoster Virus ORF61p

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